Markers of Clinical and Biological Response to Home Delivered Transcranial Alternating Current Stimulation (tACS) in Patients With Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 2
- 主要终点
- Changes in Face-Name Associative Memory Test (FNAT) scores
研究概览
简要总结
Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as "oscillopathies". Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances.
Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory.
On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease.
In this randomized, double-blind, sham-controlled study, followed by an open-label phase, the investigators will evaluate whether a 9- or 18-weeks treatment with gamma tACS over the precuneus, delivered at home, can improve symptoms in patients with mild Alzheimer's disease.
详细描述
Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as "oscillopathies". Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances.
Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory.
On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease.
In this randomized, double-blind, sham-controlled study, followed by an open-label phase, the investigators will evaluate whether a 9- or 18-weeks treatment with gamma tACS over the precuneus, delivered at home, can improve symptoms in patients with mild Alzheimer's disease.
Subjects will be randomized in two groups in the first part of the trial. One group will receive a two-months treatment with gamma tACS (40 Hz) over the precuneus while the other group will receive placebo (sham) stimulation. After two-months, both group will undergo real stimulation (open-label phase) with gamma tACS (40 Hz) over the precuneus for two-months. Modulators of response will be considered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Changes in Face-Name Associative Memory Test (FNAT) scores
时间窗: Difference between treatments (real and sham) at week 8
The Face-Name Associative Memory Test is a cross-modal associative memory test, it includes 20 face-name pairs. The administration procedure starts with the presentation of 20 faces with each name and participants should read the name underneath the faces and try to learn each face-name pair. After 5 minutes, the faces are shown one by one and participants are asked to recall the associated names from 4 different names. The correct number of pairs recalled is recorded. The score ranges from 0 (worse performance) to 20 (best performance).
Changes in Alzheimer's Disease Assessment Scale Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
时间窗: Difference between treatments (real and sham) at week 8
ADCS-ADL scores range from 0 to 78, with lower scores indicating greater functional impairment.
Safety of transcranial alternating current stimulation delivered at home
时间窗: Through study completion, at week 24
Incidence of Treatment-Emergent Adverse Events as assessed by the incidence of adverse events graded from 1 (mild) to 5 (fatal).
Tolerability of transcranial alternating current stimulation delivered at home
时间窗: Through study completion, at week 24
Tolerability will be evaluated with percentage of compliance (number of delivered stimulations divided by number of programmed stimulations times one-hundred). The primary outcome will be reached if compliance will be \>90%.
Changes in Clinical Dementia Rating scale (CDR) sum of boxes
时间窗: Difference between treatments (real and sham) at week 8
CDR-SB scores range from 0 to 18, with higher scores indicating worse cognition and daily function.
Changes in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)13
时间窗: Difference between treatments (real and sham) at week 8
ADAS-Cog13 scores range from 0 to 85, with higher scores indicating a greater deficit.
次要结局
- Changes in Clinical Dementia Rating scale (CDR) sum of boxes(Change from baseline to week 8 - 16 - 24)
- Changes in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)13(Change from baseline to week 8 - 16 - 24)
- Changes in the Neuropsychiatric Inventory (NPI-Q)(Change from baseline to week 8 - 16 - 24)
- Changes in Rey Auditory Verbal Learning Test scores(Change from baseline to week 8 - 16 - 24)
- Changes in Face-Name Associative Memory Test (FNAT) scores(Change from baseline to week 8 - 16 - 24)
- Changes in Caregiver Burden Inventory (CBI)(Change from baseline to week 8 - 16 - 24)
- Changes in Alzheimer's Disease Assessment Scale Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)(Change from baseline to week 8 - 16 - 24)
- Change in SAI measurements(Change from baseline to week 8 - 16 - 24)
- Change in EEG gamma power(Change from baseline to week 8 - 16 - 24)
- Change in plasma NfL levels(Change from baseline to week 8 - 16 - 24)
- Change in plasma GFAP levels(Change from baseline to week 8 - 16 - 24)
- Change in plasma amyloid beta1-40 levels(Change from baseline to week 8 - 16 - 24)
- Change in plasma amyloid beta1-42 levels(Change from baseline to week 8 - 16 - 24)
- Change in plasma pTau217(Change from baseline to week 8 - 16 - 24)
- Change in resting state MRI connectivity(Change from baseline to week 8)
- Change in plasma TMT part B scores(Change from baseline to week 8 - 16 - 24)
- Changes in semantic fluency task(Change from baseline to week 8 - 16 - 24)
研究者
Barbara Borroni
Prof.
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia